Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway
Abstract Annexin A5 (ANXA5) is a small calcium-dependent protein that binds specifically to negatively charged phosphatidylserine as a marker of apoptosis. Previous studies have shown that ANXA5 expression is elevated in hypertensive patients and is closely related to left ventricular systolic funct...
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Nature Portfolio
2024-12-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83244-3 |
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| author | Lina Zhao Hongjuan Cao Yao Yuan Chunyan Liao Dan Huang Xiaoyi Li Yueyao Zhao Quanfeng Huang Sha Li Bei Zhang |
| author_facet | Lina Zhao Hongjuan Cao Yao Yuan Chunyan Liao Dan Huang Xiaoyi Li Yueyao Zhao Quanfeng Huang Sha Li Bei Zhang |
| author_sort | Lina Zhao |
| collection | DOAJ |
| description | Abstract Annexin A5 (ANXA5) is a small calcium-dependent protein that binds specifically to negatively charged phosphatidylserine as a marker of apoptosis. Previous studies have shown that ANXA5 expression is elevated in hypertensive patients and is closely related to left ventricular systolic function in hypertensive patients, but its specific mechanism of action has not been clarified. GEO database analysis showed that ANXA5 expression was significantly upregulated in hypertensive myocardial hypertrophy. The expression of ANXA5 protein and mRNA was overexpressed, and knockdown of ANXA5 can effectively attenuate cardiomyocyte apoptosis and inflammatory response, ameliorate myocardial hypertrophy and cardiac dysfunction in ALD-induced hypertrophic cardiomyocytes and in SHR hypertrophic hearts. Mechanistically, ANXA5 has synergistic effect with intracellular calciumion level. In the meantime, ANXA5 knockdown inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. It should be noted that LY290004 (PI3K/Akt signaling pathway inhibitor) can weaken the inhibitory effect of knockdown ANXA5 on cardiomyocyte apoptosis and myocardial protection. Therefore, ANXA5 knockdown improves hypertensive myocardial hypertrophy and cardiac function by inhibiting apoptosis and inflammatory response and activating PI3K/AKT/Bcl-2 pathway, ANXA5 may be a potential therapeutic direction for the treatment of hypertensive myocardial hypertrophy. |
| format | Article |
| id | doaj-art-efbbecbd88a44f8d9b4425a6d23d4a48 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-efbbecbd88a44f8d9b4425a6d23d4a482025-01-05T12:27:46ZengNature PortfolioScientific Reports2045-23222024-12-0114111510.1038/s41598-024-83244-3Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathwayLina Zhao0Hongjuan Cao1Yao Yuan2Chunyan Liao3Dan Huang4Xiaoyi Li5Yueyao Zhao6Quanfeng Huang7Sha Li8Bei Zhang9Guizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityGuizhou Medical UniversityDepartment of Ultrasound Center, The Affiliated Hospital of Guizhou Medical UniversityGuizhou Medical UniversityAbstract Annexin A5 (ANXA5) is a small calcium-dependent protein that binds specifically to negatively charged phosphatidylserine as a marker of apoptosis. Previous studies have shown that ANXA5 expression is elevated in hypertensive patients and is closely related to left ventricular systolic function in hypertensive patients, but its specific mechanism of action has not been clarified. GEO database analysis showed that ANXA5 expression was significantly upregulated in hypertensive myocardial hypertrophy. The expression of ANXA5 protein and mRNA was overexpressed, and knockdown of ANXA5 can effectively attenuate cardiomyocyte apoptosis and inflammatory response, ameliorate myocardial hypertrophy and cardiac dysfunction in ALD-induced hypertrophic cardiomyocytes and in SHR hypertrophic hearts. Mechanistically, ANXA5 has synergistic effect with intracellular calciumion level. In the meantime, ANXA5 knockdown inhibited cell apoptosis along with a decrease of Bax/Bcl-2 ratio, and induction of PI3K/AKT activation. It should be noted that LY290004 (PI3K/Akt signaling pathway inhibitor) can weaken the inhibitory effect of knockdown ANXA5 on cardiomyocyte apoptosis and myocardial protection. Therefore, ANXA5 knockdown improves hypertensive myocardial hypertrophy and cardiac function by inhibiting apoptosis and inflammatory response and activating PI3K/AKT/Bcl-2 pathway, ANXA5 may be a potential therapeutic direction for the treatment of hypertensive myocardial hypertrophy.https://doi.org/10.1038/s41598-024-83244-3ANXA5HypertensiveMyocardial hypertrophyPI3K/Akt signaling pathway |
| spellingShingle | Lina Zhao Hongjuan Cao Yao Yuan Chunyan Liao Dan Huang Xiaoyi Li Yueyao Zhao Quanfeng Huang Sha Li Bei Zhang Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway Scientific Reports ANXA5 Hypertensive Myocardial hypertrophy PI3K/Akt signaling pathway |
| title | Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway |
| title_full | Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway |
| title_fullStr | Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway |
| title_full_unstemmed | Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway |
| title_short | Annexin A5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the PI3K/AKT/Bcl-2 signaling pathway |
| title_sort | annexin a5 knockdown inhibits cardiomyocyte apoptosis and alleviates cardiac hypertrophy via activating the pi3k akt bcl 2 signaling pathway |
| topic | ANXA5 Hypertensive Myocardial hypertrophy PI3K/Akt signaling pathway |
| url | https://doi.org/10.1038/s41598-024-83244-3 |
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